NC_000011.10:g.2171856C>T AND Autosomal recessive DOPA responsive dystonia

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Mar 25, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001390236.18

Allele description [Variation Report for NC_000011.10:g.2171856C>T]

NC_000011.10:g.2171856C>T

Gene:

TH:tyrosine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NC_000011.10:g.2171856C>T

HGVS:

NC_000011.10:g.2171856C>T
NG_008128.1:g.4950G>A
NC_000011.9:g.2193086C>T
NM_199292.2:c.-70G>A

Nucleotide change:

-70G-A

Links:

OMIM: 191290.0010; dbSNP: rs1372180906

NCBI 1000 Genomes Browser:

rs1372180906

Condition(s)

Name:: Autosomal recessive DOPA responsive dystonia
Synonyms:: Segawa syndrome, autosomal recessive; DYT-TH; TH-deficient dopa-responsive dystonia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011551; MedGen: C2673535; Orphanet: 101150; OMIM: 605407

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033373	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2007)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 17696123, 9235905
SCV001591903	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17696123, 21465550, 28492532
SCV004203869	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 25, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000033373

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2007)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001591903

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 21, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004203869

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 25, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Structure/function relationship of the cAMP response element in tyrosine hydroxylase gene transcription.

Tinti C, Yang C, Seo H, Conti B, Kim C, Joh TH, Kim KS.

J Biol Chem. 1997 Aug 1;272(31):19158-64.

PubMed [citation]

PMID:: 9235905

Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene.

Verbeek MM, Steenbergen-Spanjers GC, Willemsen MA, Hol FA, Smeitink J, Seeger J, Grattan-Smith P, Ryan MM, Hoffmann GF, Donati MA, Blau N, Wevers RA.

Ann Neurol. 2007 Oct;62(4):422-6.

PubMed [citation]

PMID:: 17696123

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000033373.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 4 affected members of 2 unrelated families with Segawa syndrome (605407), Verbeek et al. (2007) identified a homozygous -70G-A transition in the promoter region of the TH gene. The mutation occurred within a conserved consensus sequence of the cAMP response element. Site-directed mutagenesis of the cAMP response element in the rat promoter region showed significantly decreased basal TH expression (Tinti et al., 1997).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591903.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 526213). This variant has been observed in individual(s) with tyrosine hydroxylase deficiency (PMID: 17696123, 21465550; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant occurs in a non-coding region of the TH gene. It does not change the encoded amino acid sequence of the TH protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004203869.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine